Theodora Duka

Attentional bias associated with alcohol cues: differences between heavy and occasional social drinkers

Abstract.Rationale: Previous research has shown an attentional bias toward drug-related stimuli in opiate addicts and toward emotionally threatening words in anxiety patients. Objective: The primary aim of this study was to investigate whether non-dependent heavy social drinkers would differ in their selective attention towards alcohol-related stimuli in comparison with a group of occasional social drinkers. Methods: Attentional bias was assessed using alcohol-related pictures and words in a dot probe detection task. Picture and word pairs were visually presented, followed by a dot probe that replaced one of the items. Attentional bias was determined from latencies in responding to the dot probe. Questionnaires were used to examine the relationships among attention, outcome expectancies after alcohol consumption, and personality traits. Higher-order executive function was also measured with two cognitive tasks, recognition memory and attentional shift. Results: The heavy social drinkers showed an attentional bias towards the alcohol-related stimuli when compared to the occasional social drinkers. The heavy social drinkers also scored more highly on expectancy factors of sociability and sexuality and lower on the personality traits of self-directedness and persistence. Conclusion: The results support cognitive theories of addictive behaviour in which the ability of drug-related stimuli to capture attention is suggested to play a part in drug dependence, craving and relapse.

The effects of 3-week estrogen hormone replacement on cognition in elderly healthy females.

Abstract Rationale: Estrogen concentrations decline with age and menopause is often followed by an acceleration of the age effects on cognition. It is suggested that replacement of estrogen would reinstate, at least in part, cognitive abilities. Effects of estrogens on memory have been reported in studies with women in a clinical setting who either needed or wished to have the estrogen replacement and are mostly in the perimenopausal age-band. Objective: The present study investigated the effects of estradiol on memory and on frontal lobe function in elderly female subjects who did not suffer any of the postmenopausal symptoms and had never taken estrogen hormone replacement (EHR) previously. Methods: EHR (Progynova TS, transdermal estradiol; n=19) or placebo (n=18) was given for a period of 3 weeks to elderly healthy female subjects. Memory, frontal lobe functions (inhibition and planning) and visuospatial abilities (mental rotation) were tested before and after treatment. Estrogen plasma levels were measured to confirm the result of EHR. Cortisol plasma levels were also measured before and after cognitive performance in order to evaluate the effects of EHR on the sensitivity of the hypothalamo- pituitary-adrenal (HPA) axis to mild mental stress. Results: Plasma estradiol levels in the drug group increased to levels equivalent to that of a fertile woman (0.21± 0.5 nmol/l). Memory function as well as visuospatial abilities as measured by a mental rotation task improved significantly with EHR. However, there was no effect of EHR on frontal lobe functions. The cognitive effects were not dependent on an improvement in mood or general well-being as may be the case with EHR in women at peri- or post-menopausal stage. EHR was found to increase the HPA response to task-induced stress, as indicated by an increase in cortisol plasma levels. Conclusions: The present study has provided evidence of a beneficial effect of EHR on cognitive abilities given for first time to healthy elderly women. Furthermore, the present study has demonstrated a differential effect of EHR on memory, visuospatial abilities and frontal lobe function.

Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex

Binge drinking is an increasingly recognized problem within the UK. We have studied the relationship of binge drinking to cognitive and emotional functioning in young adults, and have found evidence for increased impulsivity, impairments in spatial working memory and impaired emotional learning. Since in human studies it is difficult to understand whether such behavioural changes pre-date or are a consequence of binge drinking, we have also studied parallel behaviours in a rodent model, in which rats are exposed to intermittent episodes of alcohol consumption and withdrawal. In this model, and in parallel with our findings in human binge drinkers, and alcoholic patients who have undergone multiple episodes of detoxification, we have found evidence for impairments in aversive conditioning as well as increased impulsivity. These behavioural changes are accompanied by facilitated excitatory neurotransmission and reduced plasticity (long-term potentiation (LTP)) in amygdala and hippocampus. The impaired LTP is accompanied by both impaired associative learning and inappropriate generalization of previously learned associations to irrelevant stimuli. We propose that repeated episodes of withdrawal from alcohol induce aberrant neuronal plasticity that results in altered cognitive and emotional competences.

Experimental manipulation of attentional biases in heavy drinkers: do the effects generalise?

RationaleIn heavy drinkers, training attention towards alcohol cues increases alcohol craving, but it is not clear if effects of ‘attentional training’ generalise to novel stimuli and measurement procedures.ObjectivesWe investigated possible generalisation of attentional training to novel alcohol cues and other methods of measuring cognitive bias.Materials and methodsA modified visual probe task was used to train participants to direct their attention either towards (‘attend alcohol’ group) or away from (‘avoid alcohol’ group) alcohol cues; attentional bias was not manipulated in a control group (total N = 60). After attentional training, we measured cognitive bias (using visual probe, modified Stroop, flicker-induced change blindness and stimulus–response compatibility tasks), alcohol craving and alcohol consumption.ResultsAttentional bias for alcohol cues increased in the ‘attend alcohol’ group, and this effect generalised to novel stimuli, but not to other cognitive bias tasks. In the ‘avoid alcohol’ group, attentional bias was reduced for the stimuli that were used during attentional training, but these effects did not generalise to different stimuli or cognitive bias tasks. Alcohol craving increased among participants in the ‘attend alcohol’ group, but only among participants who were aware of the experimental contingencies during attentional training. There were no group differences in alcohol consumption.ConclusionsThe effects of attentional training show limited generalisation to different alcohol cues and methods of measuring cognitive bias. Experimentally increased attentional bias seems to increase subjective craving, but only among participants who are aware of the experimental contingencies that were in place during attentional training.

Impairment in Cognitive Functions After Multiple Detoxifications in Alcoholic Inpatients

BACKGROUND Repeated experience of withdrawal from alcohol results in a kindling-like process leading to increased likelihood and severity of convulsions during detoxification. The aim of this study was to determine whether repeated withdrawals affect cognitive function. METHODS We investigated alcoholic patients undergoing detoxification in an inpatient setting, using tasks sensitive to dysfunction of prefrontal areas. The tasks applied were two maze tasks from the Wechsler Intelligence Scale for Children, the color Stroop task, and the vigilance task for adults and the delay task from the Gordon Diagnostic System. Forty-two abstinent alcoholic patients who were no longer receiving pharmacotherapy for detoxification participated. RESULTS Compared to a group of forty-three social drinkers matched for age, sex, and verbal IQ, the alcoholic patients took more time to complete maze 1 and made more errors in both mazes. Alcoholics made more commission errors and gave fewer correct answers in the vigilance task. No differences were found in the color Stroop task between alcoholic patients and social drinkers. Patients with 2 or more detoxifications were more impaired in the maze 1, in the vigilance task and in the delay task than patients with a single, or no previous detoxification. When patients were reclassified on the basis of the total number of attempts at withdrawing from alcohol (including the medically supervised) only the deficit in the vigilance task was associated with the number of withdrawal attempts. The effects of medically supervised detoxifications on maze 1 and vigilance task were confounded with other factors related to the history of alcoholism, alcohol use, age of starting heavy drinking and years of problem drinking. CONCLUSIONS Repeated experience of withdrawal from alcohol is thus associated with impaired cognitive function although it appears that for some of these effects, other factors associated with the history of alcoholism might also be involved.

Consequences of Multiple Withdrawals From Alcohol

This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL, organized by Theodora Duka and chaired by Dai Stephens. The purpose of the symposium was to examine the effects of multiple experiences of withdrawal from alcohol in animals made dependent on alcohol and in humans who are alcohol dependent. Parallels were drawn to the effects of repeated short-lived high-content alcohol exposures in animals and in humans who are social drinkers but indulge in binge drinking. The presentations were (1) Multiple detoxifications and risk of relapse in abstinent alcoholics, by John Gentry and Robert Malcolm; (2) Emotional and cognitive impairments after long-term use of alcohol: relationship to multiple detoxifications and binge drinking, by Theodora Duka; (3) The effect of repeated withdrawal from ethanol on conditioning to appetitive stimuli, by Tamzin Ripley, Gilyanna Borlikova, and Dai Stephens; (4) Alcohol withdrawal kindling: electrographic measures in a murine model of behavioral seizure sensitization, by Lynn Veatch and Howard Becker; and (5) Binge drinking induced changes in CNS, by Fulton Crews.

Impairment of cognitive abilities and decision making after chronic use of alcohol: the impact of multiple detoxifications.

AIMS In the present study, the effect of previous detoxifications on prefrontal function and decision making was examined in alcohol-dependent patients. Further, we examined whether the length of abstinence affects cognitive function. METHODS Forty-eight alcohol-dependent patients were recruited from an inpatient detoxification treatment facility and cognitive function was compared to a control group of 36 healthy controls. The patient population was then divided into a group of patients with less than two previous detoxifications (LO-detox group, n = 27) and a group of patients with two or more previous detoxifications (HI-detox group, n = 21) and cognitive function was compared. In addition, cognitive function of recently (i.e. less than 16 days; median split) and longer abstinent patients was compared. We assessed prefrontal function, memory function and intelligence. RESULTS Alcoholics, when compared to healthy controls, performed worse with regard to the performance index Attention/Executive function. Cognitive impairment in these tasks was pronounced in recently abstinent patients. We found no significant differences between HI-detox and LO-detox patients with regard to the Attention/Executive function. However, in the IOWA gambling Task, the HI-detox group seemed to be less able to learn to choose cards from the more advantageous decks over time. CONCLUSIONS Our results provide additional evidence for cognitive impairment of alcohol-dependent patients with regard to tasks sensitive to frontal lobe function and underline the importance of abstinence for these impairments to recover. We found only little evidence for the impairing effects of repeated withdrawal on prefrontal function and we suggest that executive function is affected earlier in dependence.

Behavioural measures of frontal lobe function in a population of young social drinkers with binge drinking pattern

BACKGROUND Binge drinking may lead to brain damage. The aim of the present study was to compare the cognitive abilities of binge and non-binge drinkers in tasks which test functions linked to discrete areas of the prefrontal cortex. METHODS Non-binge and binge drinkers were identified according to their binge score derived from the Alcohol Use Questionnaire. Cognitive performance was tested with the Spatial Working Memory task (SWM) linked to the dorsolateral prefrontal cortex, Intra/Extradimensional Shift and reversal task (IED) linked to dorsolateral prefrontal cortex (shift) and to orbitofrontal cortex (reversal), Paired Associates Learning task (PAL) linked to temporal cortex, and Reaction Time Task (RTI) a task measuring motor impulsivity (Inferior frontal gyrus). Personality traits, alcohol outcome expectancies and mood were also evaluated. RESULTS Binge drinkers recorded a significantly shorter movement time to target in the RTI, and completed fewer stages on first trial in the PAL, compared with non-bingers. In the IED as well as in the SWM, only female binge drinkers were more impaired than non-binge drinkers. CONCLUSIONS Functions linked to dorsolateral prefrontal cortex may be more impaired in female, whereas functions linked with the temporal lobe may be impaired in both male and female binge drinkers compared to non-binge drinkers. Functions linked to orbitofrontal cortex were not impaired. The increased speed of response in the RTI in binge drinkers may indicate an increased motor impulsivity in binge drinkers.

Cue reactivity in smokers: the effects of perceived cigarette availability and gender

We examined the effects of perceived cigarette availability and gender on smoking cue reactivity. Smokers were exposed to smoking cues (smoking paraphernalia) and control cues whilst their subjective and physiological responses were measured. Perceived cigarette availability was manipulated on a between-subjects basis before cue exposure. Relative to control cues, smoking cues evoked increases in the level of skin conductance in all participants. Cigarette craving was also increased in the presence of smoking cues, but only in female participants. Perceived cigarette availability had no effect on these responses. Participants also showed salivary reactivity to smoking cues, with males showing a decrease in salivation, and females showing an increase, but only when cigarettes were perceived as unavailable. These results suggest that perceived cigarette availability may not influence craving and skin conductance reactivity to smoking cues in minimally dependent smokers who are not nicotine deprived. In addition, the present data suggest that there are important gender differences in craving reactivity to smoking cues.

Repeated ethanol exposure and withdrawal impairs human fear conditioning and depresses long-term potentiation in rat amygdala and hippocampus.

BACKGROUND In rats, repeated episodes of alcohol consumption and withdrawal (RWD) impair fear conditioning to discrete cues. METHODS Fear conditioning was measured in human binge drinkers as the increased startle response in the presence of a CS+ conditioned to aversive white noise. Secondly, the ability of tone CSs, paired with footshock, to induce c-fos expression, a marker of neuronal activity, in limbic structures subserving emotion was studied in rats. Additionally, consequences of RWD on subsequent induction of long term potentiation (LTP) in external capsule/lateral amygdala and Schaffer collateral/hippocampus CA1 pathways were studied in rat brain slices. RESULTS Fear conditioning was impaired in young human binge drinkers. The ability of fear-conditioned CSs to increase c-fos expression in limbic brain areas was reduced following RWD, as was LTP induction. Rats conditioned prior to RWD, following RWD showed generalization of conditioned fear from the tone CS+ to a neutral control stimulus, and a novel tone. CONCLUSIONS Binge-like drinking impairs fear conditioning, reduces LTP, and results in inappropriate generalization of learned fear responses. We propose a mechanism whereby RWD-induced synaptic plasticity reduces capacity for future learning, while allowing unconditioned stimuli access to neuronal pathways underlying conditioned fear.